Clinical Analysis Of Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease

ObjectiveTo analyze the clinical manifestations,cerebrospinal fluid and imaging features of myelin oligodendrocyte glycoprotein antibody-associated disease(MOG-AD)and compare with aquaporin-4(AQP-4)positive neuromyelitis optica spectrum disease(NMOSD).Compare clinical data of children and adults with MOG-AD.Summarize the clinical features of MOG-AD,with a view to improving clinical understanding of MOG-AD.Materials and MethodsClinical data of patients hospitalized in the Department of Neurology,Pediatrics and Ophthalmology of Qilu Hospital of Shandong University from August 2017 to January 2020 were collected,and a total of 29 patients with MOG-AD and 31 patients with AQP-4 positive NMOSD that met the inclusion criteria were screened.The clinical data of all patients were collected.At the same time,the patients of MOG-AD group with age<18 years were classified as M-child group,and those with age?18 years were classified as M-adult group.All enrolled patients were followed up for a period of 3-30 months to observe the recurrence of the disease during the follow-up period,and all patients were treated with an expanded disability status scale(EDSS)before regular medication in the acute phase.Results1.Baseline characteristics:There were 29 patients in the MOG-AD group and 31 patients in the AQP-4 positive NMOSD group.Males were more common in the MOG-AD group(55.17%),while the AQP-4 positive NMOSD group was dominated by females(70.97%).The difference between the two groups was statistically significant(P=0.04).The average age of onset in the MOG-AD group was(34.72 ±18.58)years.The average age of the first attack in the AQP-4 positive NMOSD group was(42.29± 15.63)years,and there was no significant difference in the average age of onset between the two groups(P=0.092).The M-child group accounts for 20.69%(6/29)and the M-adult group accounts for 79.31%(23/29).2.Clinical characteristics:? Disease course:7 patients(24.14%)with MOG-AD showed a recurrent disease course,and 13 patients(41.94%)with AQP-4 positive NMOSD relapsed.?Precursor history:9 patients with MOG-AD had a history of infection before the onset of disease,and a 2-year-old child had a history of vaccination 2 weeks before onset.Three patients with AQP-4 positive NMOSD had a history of respiratory tract infection before onset,and one patient was in puerperium.?Clinical phenotype:In the first episode,patients in the MOG-AD group with an acute demyelinating encephalomyelitis(ADEM)like phenotype were more common than the AQP-4 positive NMOSD group(P=0.009),while the differences between optic neuritis,myelitis,encephalitis/brain stem encephalitis were not statistically significant.Two patients with MOG-AD showed cortical encephalitis,which was not seen in the AQP-4 positive NMOSD group.The ADEM-like phenotype was more common in children than in adults(P<0.01),and was the main phenotype of MOG-AD in children(83.33%).3.Radiological features:?Optic nerve Magnetic Resonance Imaging(MRI):9 patients with MOG-AD underwent optic nerve MRI in the acute phase,7 patients of which were abnormal,4 patients had bilateral optic nerve involvement,and 4 patients had long segmental lesions.The lesions of 5 cases were located in the retrobulbar segment of optic nerve,1 case was located in the optic chiasm,and 1 case was located in the optic tract.Seven patients with AQP-4 positive NMOSD had optic nerve MRI,and five were abnormal.Among them,two patients had bilateral optic nerve involvement and only one patient had optic nerve posterior segment involvement.There was no statistically significant difference in optic nerve lesions between the two groups(P>0.05).?Brain MRI:27 patients with MOG-AD underwent brain MRI and 17 of them had intracranial lesions.The lesions were as follows:2 cases of cortex,10 cases of subcortical,9 cases of lateral ventricle,5 cases of basal ganglia,4 cases of corpus callosum,2 cases of cerebellum,4 cases of midbrain,5 cases of pons,and 3 cases of medulla oblongata.21 patients in the AQP-4 positive NMOSD group underwent craniocerebral MRI and 12 of which had intracranial lesions.The lesions were as follows:4 cases of subcortical,3 cases of paraventricular,2 cases of basal ganglia,1 case of corpus callosum,1 case of cerebellum,2 cases of midbrains,1 case of pons,and 8 cases of medulla oblongata.There was no statistical difference in the distribution of brain lesions between the two groups(P>0.05).?Spinal MRI:Spinal MRI was performed in 16 patients with MOG-AD,and 12 of them had lesions in the spinal cord.7 cases had long-segment lesions(?3 spinal cord segments),and 5 cases had multiple segment lesions.The involved sites were as follows:6 cases of cervical spinal cord,7 cases of thoracic spinal cord,and 5 cases of lumbar spinal cord.22 patients with AQP-4 positive NMOSD underwent MRI of the spinal cord,and 19 patients had spinal cord lesions.8 cases had long-segment lesions,and 3 cases had multiple segment lesions.The involved sites were as follows:17 cases of cervical spinal cord,12 cases of thoracic spinal cord,and 1 case of lumbar spinal cord.There were more cervical spinal lesions in the AQP-4 positive NMOSD group than in the MOG-AD group,and the difference was statistically significant(P=0.007).4.Laboratory examination:?Autoimmune markers:MOG-AD group was less complicated with other autoimmune diseases,the difference between the two groups is statistically significant(P=0.009).?Cerebrospinal fluid examination:There was no significant difference between the MOG-AD group and the AQP-4 positive NMOSD group in terms of cerebrospinal fluid pressure,white blood cell counts,protein determination,and oligoclonal band positive ratio(P>0.05).5.Treatment and prognosis:?Treatment:Among 29 patients with MOG-AD,25 patients were treated with high-dose intravenous hormone therapy in the acute phase(15-20mg/(kg·d),3-5d).All cases continued to take oral prednisone(1mg/(kg·d))during the remission,which was slowly reduced within 3-6 months according to clinical manifestations,MRI review results,or serum myelin oligodendrocyte glycoprotein antibody(MOG-IgG)titer.Among them,5 cases were treated with immunoglobulin(0.4g/(kg·d)for 5 days).The conditions of the above patients had improved to varying degrees.Four patients with mild condition were given oral prednisone only,and the symptoms were alleviated.Among the 29 patients,7 patients relapsed.3 of them were given high-dose intravenous hormone therapy again,and their condition could be controlled.The remaining 4 patients were added with immunosuppressive agents,including 1 case of azathioprine,2 cases of mycophenolate mofetil and 1 case of methotrexate.The patient with methotrexate still relapsed until the end of follow-up,and the remaining 3 cases did not relapse until the end of follow-up.31 patients with AQP-4 positive NMOSD were given high-dose intravenous hormone therapy in the acute phase.Among them,3 patients were treated with immunoglobulin in the acute phase,and oral prednisone was continued in the remission phase.13 patients relapsed.7 of them were treated with mycophenolate mofetil and 3 of them were treated with azathioprine.3 patients were given high-dose intravenous hormone therapy again.All of them improved.?EDSS before regular medication:The average EDSS score before treatment in the MOG-AD group was(4.28 ± 1.10),and(5.13 ± 1.12)in the AQP-4 positive NMOSD group.The difference between the two groups was significant(P=0.004),and the clinical symptoms of the MOG-AD group were milder.Conclusion1.Compared with AQP-4 positive NMOSD patients,male patients with MOG-AD are more common.2.The clinical phenotypes of MOG-AD mainly include optic neuritis,longitudinally extensive transverse myelitis(LETM),encephalitis or brainstem encephalitis,ADEM,etc.,and can also be manifested as cortical encephalitis or isolated cranial nerve involvement.The clinical phenotype is related to age.The younger the onset age is,the more the clinical phenotype tends to ADEM.3.Compared with AQP-4 positive NMOSD,MOG-AD is more prone to intracerebral lesions.Most of the spinal cord lesions are long segments or multiple long or short segments,and they are likely to involve the lower spinal cord.4.MOG-AD is rarely associated with other autoimmune diseases,such as Hashimoto's thyroiditis,systemic lupus erythematosus and Sjogren syndrome.5.Serum MOG-IgG antibody detection has higher sensitivity than cerebrospinal fluid.6.High-dose intravenous hormone therapy and immunoglobulin treatment are effective for patients with MOG-AD.For patients with clinical relapse,immunosuppressive agents such as mattemycophenate and azathioprine can be added,but some patients still have relapses.